Methods for the delivery of therapeutics, tracking dyes, genes and other substances into complex neural tissue, organotypic cultures and cell types are limited in their effectiveness. The biolistic process, based on acceleration of carrier particles to sufficient velocity, has recently been shown to be a relatively effectual delivery method for neuronal systems. Cell damage and tissue death mediated by the current delivery devices however, limit more widespread use of this process, especially for clinical applications. We propose in this Phase II program, in collaboration with our STTR partner, to expand upon our Phase I development of a novel ballistic device that can be used for delivery of materials to micro-targeted areas, as small as 25 5m, in cells and tissues with minimal trauma. We improved the device design during Phase I so that precise doses of carrier particles and molecules are reproducibly delivered to defined spatial regions. As part of Phase II, additional functional improvements to the device such as a fully automated version will enable high-throughput, programmable, targeted delivery to neural tissues and cells. At the end of our Phase II research we will have developed a modular device that allows the end-user to reproducibly deliver a specified dose of a macromolecule of interest to a pre-selected defined target using a single device. Importantly, this device will have been demonstrated to be effective for delivery in a variety of biological model systems. The use of this system will aid neurobiologists in their understanding of brain development and function, be of use to scientists focusing on cell biology, plants, and other related fields, and be a valuable tool for medical researchers for the delivery of diagnostic and therapeutic compounds. Public Health Relevance: The proposed research will lead to the further development of a novel pneumatic ballistic delivery device that can be used by the biomedical research community to enhance the basic understanding of disease processes. In addition, this product may have a direct impact on public health by enabling delivery of clinically important macromolecules to cells and tissues of interest.